To obtain more precise knowledge of the mechanism of antibody biosynthesis the heavy chains of rabbit antibodies provide particularly suitable material. Their variable regions contain both amino acid replacement associated with genetic markers and those associated with immunological specificity. The relationship between these two types of variation and in turn the relationship of the variable region to the constant sequences specifying heavy chain classes are critical to the understanding of the immune mechanism. These relationships will be pursued by the use of the following approaches: 1) Identification of the allotypic amino acid replacements with the antigenic differences which distinguish the a locus phenotypes of the heavy chains 2) Identification of the active site residues in homogeneous antibody by affinity labelling with the reactive carbene group and location of these residues relative to the genetic determinants 3) Analysis of conformational changes in the heavy chain constant regions induced by hapten binding in the variable region. 4) Investigations of the role of J chain in determining the structure and biological properties of IgA and IgM antibodies.